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Bacterial meningitis in children older than one month: Clinical

features and diagnosis
Author: Sheldon L Kaplan, MD
Section Editors: Morven S Edwards, MD, Douglas R Nordli, Jr, MD
Deputy Editor: Carrie Armsby, MD, MPH

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Mar 2020. | This topic last updated: Aug 15, 2018.

INTRODUCTION

Meningitis is an inflammatory disease of the leptomeninges, the tissues surrounding the brain and spinal cord.
The meninges consist of three parts: the pia, arachnoid, and dura mater. Meningitis reflects inflammation of the
arachnoid mater and the cerebrospinal fluid (CSF) in both the subarachnoid space and in the cerebral
ventricles.

Suspected bacterial meningitis is a medical emergency, and immediate diagnostic steps must be taken to
establish the specific cause so that appropriate antimicrobial therapy can be initiated. The mortality rate of
untreated bacterial meningitis approaches 100 percent. Even with optimal therapy, morbidity and mortality may
occur. Neurologic sequelae are common among survivors.

The clinical and laboratory features of bacterial meningitis in infants and children older than one month will be
reviewed here. The treatment and prognosis of bacterial meningitis in infants and children are discussed
separately, as are the epidemiology and pathogenesis of bacterial meningitis and the clinical features,
diagnosis, treatment, and prognosis of bacterial meningitis in neonates (<1 month of age) and adults:

● (See "Bacterial meningitis in children older than one month: Treatment and prognosis".)
● (See "Pathogenesis and pathophysiology of bacterial meningitis".)
● (See "Bacterial meningitis in the neonate: Clinical features and diagnosis".)
● (See "Bacterial meningitis in the neonate: Treatment and outcome".)
● (See "Clinical features and diagnosis of acute bacterial meningitis in adults".)
● (See "Initial therapy and prognosis of bacterial meningitis in adults".)

EPIDEMIOLOGY

After the introduction of the Haemophilus influenzae type b (Hib) and pneumococcal conjugate vaccines to the
infant immunization schedule (in 1990 and 2000, respectively) the incidence of bacterial meningitis declined in
all age groups except children younger than two months [1]. The median age shifted from <5 years to 42 years
[1,2]. The peak incidence continues to occur in children younger than two months.

In population-based surveillance (2006 to 2007), the incidence of bacterial meningitis in United States children
varied with age [1]:
 ● <2 months – 80.69 per 100,000 population
● 2 through 23 months – 6.91 per 100,000 population
● 2 through 10 years – 0.56 per 100,000 population
● 11 through 17 years – 0.43 per 100,000 population

Causative organisms — The organisms responsible for acute bacterial meningitis depend in part upon the
route of acquisition and underlying host factors (table 1 and table 2).

The relative frequency of pathogens causing bacterial meningitis in children changed after the introduction of
the Hib and pneumococcal conjugate vaccines to the routine childhood immunization schedule (figure 1) [3]. In
a retrospective review of 231 cases of bacterial meningitis in children (1 month through 18 years of age) who
presented to 20 pediatric emergency departments in the United States between 2001 and 2004, the most
frequent pathogens varied according to age, as follows:

● ≥1 month and <3 months – Group B streptococcus (39 percent), gram-negative bacilli (32 percent),
Streptococcus pneumoniae (14 percent), Neisseria meningitidis (12 percent)

● ≥3 months and <3 years – S. pneumoniae (45 percent), N. meningitidis (34 percent), group B
streptococcus (11 percent), gram-negative bacilli (9 percent)

● ≥3 years and <10 years – S. pneumoniae (47 percent), N. meningitidis (32 percent)

● ≥10 years and <19 years – N. meningitidis (55 percent)

Similar findings were noted in 587 cases of bacterial meningitis in children (0 to 18 years) identified through the
Emerging Infections Program Network between 1998 and 2007 [1].

Before widespread vaccination for Hib in the United States, Hib was the major cause of bacterial meningitis in
children [4]. Although the incidence of pneumococcal meningitis in children in the United States declined by 55
to 60 percent after widespread vaccination for S. pneumoniae, S. pneumoniae remains the most frequent cause
of bacterial meningitis in children [1,3,5-7]. Even with prompt and appropriate therapy, pneumococcal meningitis
is an important cause of childhood morbidity and mortality [3]. (See "Pneumococcal meningitis in children",
section on 'Outcome'.)

Predisposing factors — In addition to specific factors that may predispose certain hosts to bacterial meningitis
with a particular organism (table 2), the following factors also may increase the risk of bacterial meningitis [8]:

● Recent exposure to someone with meningococcal or Hib meningitis

● Recent infection (especially respiratory or otic infection)

● Recent travel to areas with endemic meningococcal disease, such as sub-Saharan Africa

● Penetrating head trauma

● Cerebrospinal fluid (CSF) otorrhea (including congenital defects, such as Mondini dysplasia) or CSF
rhinorrhea

● Cochlear implant devices, particularly those with a positioner (see "Cochlear implant infections", section on
'Risk of meningitis')

● Anatomic defects (eg, dermal sinus (picture 1) or urinary tract anomaly) or recent neurosurgical procedure
(eg, ventricular shunt placement) may predispose to meningitis with Staphylococcus aureus, coagulase-
 negative staphylococcus, and enteric gram-negative organisms, such as Escherichia coli and Klebsiella
species [9]. (See "Gram-negative bacillary meningitis: Epidemiology, clinical features, and diagnosis".)

CLINICAL FEATURES

Course — Acute bacterial meningitis has two patterns of presentation [10,11]. In the first, meningitis develops
progressively over one or several days and may be preceded by a febrile illness. In the second, the course is
acute and fulminant, with manifestations of sepsis and meningitis developing rapidly over several hours [10].
The rapidly progressive form is frequently associated with severe brain edema.

Presentation — Most patients with bacterial meningitis present with fever and symptoms and signs of
meningeal inflammation (nausea, vomiting, irritability, anorexia, headache, confusion, back pain, and nuchal
rigidity) [12-14]. These findings are often preceded by symptoms of upper respiratory infection [15]. However,
the clinical manifestations of bacterial meningitis are variable and nonspecific; no single sign is pathognomonic
[10,13]. Previous receipt of oral antibiotics does not affect the clinical presentation of acute bacterial meningitis.

The symptoms and signs depend, to some extent, upon the duration of illness, the host response to infection,
and the age of the patient [10]. The triad of fever, neck stiffness, and mental status changes is present in only
44 percent of adults with bacterial meningitis [7], and in even fewer children.

● Older children – In older children, clinical manifestations may include [10,14,16]:

• Fever
• Headache
• Photophobia
• Nausea/vomiting
• Confusion
• Lethargy
• Irritability

● Infants (<1 year) – In infants, manifestations may include [10,13,16,17]:

• Fever
• Hypothermia
• Lethargy
• Respiratory distress
• Jaundice
• Poor feeding
• Vomiting
• Diarrhea
• Seizures
• Restlessness
• Irritability
• Bulging fontanel

General appearance — Children with bacterial meningitis generally appear uncomfortable. In one study of 103
children with bacterial meningitis, three-quarters of the children were toxic-appearing at the time of admission
[16].
Vital sign abnormalities (eg, tachycardia, tachypnea) are often present, particularly in young children. Patients
with acute and fulminant presentation may present with hypotension and shock.

Meningeal signs — Although meningeal signs are present at the time of admission in the majority of patients,
they are not invariably present. In one review of 1064 cases of acute bacterial meningitis in children older than
one month, 16 (1.5 percent) had no meningeal signs during their entire period of hospitalization [18]. Nuchal
rigidity may not be elicited in comatose patients or those with focal or diffuse neurologic deficits [14]. In addition,
nuchal rigidity may occur late in the course, particularly in young children.

Nuchal rigidity is manifest by the inability to place the chin on the chest, limitation of passive neck flexion, and
Kernig and Brudzinski signs.

● Kernig sign – Kernig sign is present if the patient, in the supine position with the hip and knee flexed at 90°,
cannot extend the knee more than 135° and/or there is flexion of the opposite knee (movie 1A).

● Brudzinski sign – Brudzinski sign is present if the patient, while in the supine position, flexes the lower
extremities during attempted passive flexion of the neck (movie 1B).

Signs of meningeal irritation are present in 60 to 80 percent of children with bacterial meningitis at the time of
presentation and in approximately 25 percent of children with normal cerebrospinal fluid (CSF) findings
[11,15,19]. Other causes of nuchal rigidity are discussed below. (See 'Differential diagnosis' below.)

Neurologic findings

● Altered consciousness – In one review of 235 children with bacterial meningitis, approximately 78
percent were irritable or lethargic, 7 percent were somnolent, and 15 percent semicomatose or comatose
at the time of admission [14]. Among patients with pneumococcal meningitis, 29 percent were
semicomatose or comatose at the time of admission. In another study of 103 pediatric patients with
bacterial meningitis, 28 percent had a Glasgow coma score (GCS (table 3)) ≤10 at the time of admission
[16].

The level of consciousness at the time of admission has prognostic significance [20]; patients who are
obtunded, semicomatose, or comatose at the time of admission are significantly more likely to have an
adverse outcome than those who are lethargic or somnolent [21]. (See "Bacterial meningitis in children
older than one month: Treatment and prognosis", section on 'Prognostic factors'.)

● Increased ICP – Increased intracranial pressure (ICP) may be manifest by complaints of headache in older
children and bulging fontanel or diastasis of the cranial sutures in infants [13,14]. Bulging fontanel is neither
sensitive nor specific for bacterial meningitis. In one review, bulging fontanel was present in 20 percent of
infants with meningitis, but also in 13 percent of infants with normal CSF and viral infections other than
meningitis [19]. (See "Elevated intracranial pressure (ICP) in children: Clinical manifestations and
diagnosis".)

Other signs of increased ICP that may occur in bacterial meningitis include palsies of the third, fourth, and
sixth (most common) cranial nerves. (See "Third cranial nerve (oculomotor nerve) palsy in children" and
"Fourth cranial nerve (trochlear nerve) palsy" and "Sixth cranial nerve (abducens nerve) palsy", section on
'Clinical manifestations'.)

Papilledema, which takes several days to become apparent, is an uncommon finding in acute bacterial
meningitis. The finding of papilledema should prompt evaluation for venous sinus occlusion, subdural
empyema, or brain abscess [10]. (See 'Imaging' below.)
 ● Seizures – Seizures, typically generalized, occur before admission to the hospital or within the first 48
hours of admission in 20 to 30 percent of patients with meningitis [14,22]. Seizures later in the course are
more often focal and may indicate cerebral injury [10,22-24]. (See "Bacterial meningitis in children:
Neurologic complications", section on 'Seizures'.)

A simple seizure is rarely the sole manifestation of bacterial meningitis [25]. In one series of 410
consecutive cases of documented bacterial meningitis in children 2 months to 15 years of age, 27 percent
had seizures at or before the time of presentation [25]. All of the children with bacterial meningitis who
presented with seizures had other signs or symptoms of meningitis (altered consciousness, nuchal rigidity,
petechial rash). Altered consciousness and nuchal rigidity may be difficult to assess during the post-ictal
period, particularly in infants younger than one year.

● Focal findings – In one review of 235 children with bacterial meningitis, focal neurologic findings
(hemiparesis, quadriparesis, facial palsy, visual field defects) were present at the time of admission in 16
percent of patients overall and in 34 percent of those with pneumococcal meningitis [14]. The presence of
focal neurologic signs at the time of admission correlated with persistent abnormal neurologic examination
one year after discharge and with cognitive impairment.

Focal neurologic findings also may occur late in the course of meningitis [10].

Cutaneous findings — Petechiae (picture 2) and purpura (picture 3) may occur with any of the bacterial
pathogens but are most commonly seen in N. meningitidis [10]. The lesions are usually more pronounced on
the extremities and can be preceded by an erythematous maculopapular eruption. (See "Clinical manifestations
of meningococcal infection", section on 'Rash'.)

Complications — Complications that may occur during therapy for bacterial meningitis include seizures,
increased ICP, cerebral edema, ischemia, infected subdural effusion (image 1 and picture 4), and disseminated
illness (septic arthritis, pericarditis, etc). Neurologic complications are discussed separately. (See "Bacterial
meningitis in children: Neurologic complications".)

Arthritis is most common with meningococcal disease but may occur with other infections [14]. Early in the
course of meningitis, arthritis may be related to direct invasion of the joint, whereas arthritis that develops late in
the course is considered an immune complex-mediated event. (See "Clinical manifestations of meningococcal
infection", section on 'Arthritis'.)

Pericardial effusions also may develop in patients with disseminated illness. They usually resolve during the
course of antibiotic therapy [14]. In some cases, pericardial effusions are the cause of persistent fever, and
pericardiocentesis or an open drainage procedure may be required. (See "Clinical manifestations of
meningococcal infection", section on 'Arthritis' and "Clinical manifestations of meningococcal infection", section
on 'Pericarditis'.)

EVALUATION

Overview — Suspected bacterial meningitis is a medical emergency, and immediate diagnostic steps must be
taken to establish the specific cause (table 4). Ideally, a careful history, physical examination, blood tests, and
lumbar puncture (LP) should be performed before the initiation of therapy for meningitis.

However, in fulminant cases with hypotension and end-organ failure, rapid intervention is particularly necessary;
administration of antibiotics may precede complete history, examination, and LP. In such cases, blood culture
should be obtained before administration of antibiotics, and LP performed as soon as is feasible. (See
"Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Immediate
management'.)

History — Important aspects of the history in the child with suspected bacterial meningitis include:

● The course of illness. (See 'Course' above.)

● The presence of symptoms consistent with meningeal inflammation. (See 'Meningeal signs' above.)

● The presence of seizures – Focal seizures have important prognostic implications. (See "Bacterial
meningitis in children older than one month: Treatment and prognosis", section on 'Prognosis'.)

● The presence of predisposing factors – In addition to predisposing conditions delineated in the tables (table
1 and table 2), recent respiratory or ear infection, penetrating head trauma or craniotomy, travel to an area
with endemic meningococcal disease, exposure to someone with bacterial meningitis, cochlear
implantation device, or anatomic defects (eg, dermal sinus or urinary tract anomaly). (See 'Predisposing
factors' above.)

● Immunization history (particularly the H. influenzae type b [Hib] conjugate vaccine, pneumococcal
conjugate or polysaccharide vaccine, and meningococcal conjugate or polysaccharide vaccine); receipt of
a full series of any of these vaccines does not alter the need for cerebrospinal fluid (CSF) examination or
initial empiric therapy, but depending upon age, may affect the need for chemoprophylaxis or evaluation of
the immune system. (See "Prevention of Haemophilus influenzae type b infection", section on
'Postexposure chemoprophylaxis' and "Treatment and prevention of meningococcal infection" and "IgG
subclass deficiency".)

● History of drug allergies, particularly anaphylactic reactions to antibiotics, which, if present, may affect the
choice of antimicrobial therapy. (See "Bacterial meningitis in children older than one month: Treatment and
prognosis", section on 'Chemoprophylaxis'.)

● Recent use of antibiotics, which may affect the yield of blood and/or CSF culture. (See 'Interpretation of
CSF in pretreated patients' below.)

Examination — Important aspects of the examination of a child with suspected bacterial meningitis include vital
signs, general appearance, presence of meningeal signs, neurologic examination, and cutaneous examination.

● The vital signs provide clues to volume status, presence of shock, and the presence of increased
intracranial pressure (ICP). The constellation of systemic hypertension, bradycardia, and respiratory
depression (Cushing triad) is a late sign of increased ICP. (See "Elevated intracranial pressure (ICP) in
children: Clinical manifestations and diagnosis".)

● Head circumference should be measured at the time of admission in children younger than 18 months of
age [26]. (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on
'Monitoring'.)

● Elicitation of meningeal signs and important aspects of the neurologic and cutaneous examinations are
discussed above. (See 'Clinical features' above.)

● Patients with acute bacterial meningitis may also have clinical manifestations of other bacterial infections
(eg, facial cellulitis, sinusitis, otitis media, arthritis, pneumonia).

LABORATORY EVALUATION
Blood tests — Initial blood tests should include a complete blood count with differential and platelet count and
two aerobic blood cultures of appropriate volume. Serum electrolytes and glucose, blood urea nitrogen, and
creatinine concentrations are helpful in determining the cerebrospinal fluid- (CSF) to-blood glucose ratio, and in
planning fluid administration. Evaluation of clotting function is especially indicated if petechiae or purpuric
lesions are noted. (See 'Glucose and protein' below and "Bacterial meningitis in children older than one month:
Treatment and prognosis", section on 'Pretreatment evaluation'.)

Blood cultures are positive in at least one-half of patients with bacterial meningitis [24,27]. In one prospective
study, blood was obtained for culture from every patient with bacterial meningitis, 44 percent of whom had
received antimicrobial therapy before evaluation [28]. Blood cultures were positive in 80 percent of children with
H. influenzae type b (Hib) meningitis, 52 percent of children with pneumococcal meningitis, and 33 percent of
children with meningococcal meningitis. Among children who were not pretreated with antibiotics, blood cultures
were positive in approximately 90 percent of children with Hib and meningococcal meningitis and 80 percent of
children with pneumococcal meningitis.

CSF examination — Analysis of the CSF is critical to the diagnosis of meningitis and the differentiation of
bacterial from other etiologies (table 5). A lumbar puncture (LP) should be performed on any child in whom,
after careful history and physical examination, the diagnosis of meningitis is suspected, unless specific
contraindications to LP are present [14]. The threshold for CSF examination should be lower in high-risk
patients (table 2). (See 'Predisposing factors' above.)

LP also should be performed in children with bacteremia and meningeal signs or persistent fever (even if they
have no meningeal signs), since bacteremia can progress to meningitis within hours [12,29]. In addition, repeat
LP may be warranted in a child whose initial CSF culture was negative but in whom clinical signs of meningitis
persist [10].

Contraindications to LP include cardiopulmonary compromise, signs of increased intracranial pressure,

papilledema, altered respiratory effort, focal neurologic signs, and skin infection over the site for LP. (See
"Lumbar puncture: Indications, contraindications, technique, and complications in children", section on
'Contraindications' and 'Predisposing factors' above.)

It is essential that antimicrobial therapy not be delayed if there is a contraindication to or inability to perform an
LP, or if the LP is delayed by the need for cranial imaging. In any of these situations, blood cultures should be
obtained and empiric antibiotics administered as soon as is possible (before the imaging study in children who
require imaging) (table 4). (See 'Initiation of empiric therapy' below and 'Imaging' below.)

Examination of the CSF should include cell count and differential, glucose and protein concentration, Gram
stain, and culture. Cytocentrifugation of CSF enhances the likelihood that laboratory personnel will detect
bacteria on Gram-stained specimens. CSF cultures should be performed in all cases of suspected bacterial
meningitis, regardless of the cell count. Early in the disease process, the CSF culture may be positive in the
absence of pleocytosis [12,30].

Interpretation of CSF — Certain laboratory findings are characteristic of bacterial meningitis and are present in
most cases (table 5). These include CSF pleocytosis with a predominance of neutrophils, elevated CSF protein,
decreased CSF glucose, the presence of an organism on CSF Gram stain, and isolation of a pathogenic
organism from the CSF and blood culture.

However, because CSF and blood cultures may be obtained at different points in time during the evolution of
the disease process, varying combinations of positive or negative cultures of blood and CSF and the presence
or absence of pleocytosis are possible [10]. Early in the course (after bacterial invasion but before the
inflammatory response), the CSF culture may be positive in the absence of pleocytosis [12,30]. In some cases,
pleocytosis is present and culture of the blood reveals a pathogen, but culture of the CSF does not. A negative
culture of the CSF does not preclude the development of meningitis hours or days after LP; if clinical signs
suggest meningitis, repeat LP may be warranted [10,12].

Cell count — The CSF white blood cell (WBC) count in acute bacterial meningitis is typically >1000
WBC/microL, with a predominance of neutrophils (table 5) [14]. However, early in the course, few or no WBCs
may be present. A CSF WBC count >6/microL is considered abnormal in children older than three months of
age [14], and >9 WBCs/microL is considered abnormal for infants 29 to 90 days [31,32].

A traumatic LP can cause small amounts of bleeding into the CSF that can interfere with interpretation of the
CSF cell count. Certain formulas can be used to aid in the interpretation of the cell count when the LP is
traumatic. When the CSF is not grossly bloody, we subtract 1 WBC for every 1000 RBCs/microL. However,
none of the formulas to "correct" the CSF WBC can be used with total confidence to exclude meningitis when
the LP is traumatic [33,34]. Children in whom the LP is traumatic should be treated presumptively for meningitis
pending results of CSF culture. (See "Bacterial meningitis in children older than one month: Treatment and
prognosis", section on 'Empiric therapy'.)

The presence of a single neutrophil in the CSF is considered abnormal [10,12]. However, this finding is not
pathognomonic for bacterial meningitis; patients with aseptic meningitis can have 30 to 90 percent neutrophils
on their initial CSF examination [10]. (See "Viral meningitis: Clinical features and diagnosis in children", section
on 'CSF studies'.)

Similarly, neither the presence nor quantity of bands (immature neutrophils) in the CSF helps to distinguish
bacterial from viral meningitis [35].

Glucose and protein — The CSF glucose in acute bacterial meningitis is <40 mg/dL in more than one-half
of cases (table 5) [14]. In addition, the ratio of the CSF to blood glucose concentration is usually depressed
(<0.6 ) [36].

The CSF protein in acute bacterial meningitis typically ranges from 100 to 500 mg/dL (table 5) [14]. The CSF
protein concentration may be increased in children with traumatic LP because of the increased protein
concentration in plasma and the release of proteins from lysed red blood cells (RBC) [37]. In children with
traumatic LP the CSF protein concentration may be corrected by subtracting 1 mg/dL for every 1000
RBCs/microL [10,37].

Gram stain — The presence of an organism on CSF Gram stain can suggest the bacterial etiology one day
or more before culture results are available. The absence of organisms on Gram stain does not exclude the
diagnosis [38]. The probability of visualizing bacteria depends upon the number of organisms present [39] and
is increased by cytocentrifugation. Broad-spectrum antimicrobial therapy should be continued until CSF culture
results are available, because Gram stain results are subject to observer misinterpretation [40]. (See "Bacterial
meningitis in children older than one month: Treatment and prognosis", section on 'Empiric therapy'.)

An organism is visualized on CSF Gram stain in approximately 90 percent of children with pneumococcal
meningitis [22] and 80 percent of children with meningococcal meningitis [41]. In contrast, the Gram stain is
positive in only one-half of patients with gram-negative bacillary meningitis and one-third of patients with listeria
meningitis [42,43].

Characteristic morphologic features of the common pathogens for bacterial meningitis in children are as follows:

● Gram-positive diplococci suggest S. pneumoniae (picture 5)

 ● Gram-negative diplococci suggest N. meningitidis (picture 6)
● Small pleomorphic gram-negative coccobacilli suggest Hib (picture 7)
● Gram-positive cocci or coccobacilli suggest group B streptococcus (picture 8)
● Gram-positive rods and coccobacilli suggest L. monocytogenes (picture 9)

Culture — Isolation of a bacterial pathogen from the CSF culture confirms the diagnosis of bacterial
meningitis. However, a negative culture of the CSF at a particular point in time does not preclude the
development of meningitis hours or days later [12,30].

In one review of 128 children with bacterial meningitis, CSF cultures were positive in 97 percent of patients who
received neither oral nor parenteral antibiotics, 67 percent of patients who received oral antibiotics, and 56
percent of patients who received parenteral antibiotics before CSF cultures were obtained [44].

Rapid diagnostic tests — Rapid diagnostic tests include molecular methods (eg, polymerase chain reaction
[PCR]) and bacterial antigen detection using latex agglutination:

● Molecular methods – Molecular methods are increasingly used to assist in the diagnosis of central nervous
system (CNS) infections. PCR of CSF and blood can be helpful for documenting meningococcal disease in
the patient with negative cultures [45]. Multiplex or panel-based nucleic acid amplification tests are now
available that test for multiple bacterial and viral pathogens simultaneously in a single CSF sample (eg,
FilmArray meningitis/encephalitis panel [BioFire]) [46-48]. These tests are highly sensitive and specific,
though false-positive and false-negative results can occur. If a multiplex panel is performed, it should be
used in conjunction with standard microbiologic tests (eg, cultures of CSF and blood). Multiplex panels do
not detect all causes of CNS infection, nor do they provide any information on antimicrobial susceptibility.
Loop-mediated isothermal amplification (LAMP) is another promising nucleic acid amplification method for
rapid detection of meningococcus in respiratory and blood samples of infected children, but it is not yet
commercially available [49]. (See "Molecular diagnosis of central nervous system infections".)

● Bacterial antigen tests – CSF latex agglutination tests add little to conventional testing with Gram stain and
culture [50,51]. These tests should be reserved for cases in which the initial CSF Gram stain is negative
and CSF culture is negative at 48 hours of incubation [50].

Interpretation of CSF in pretreated patients — Prior administration of antimicrobial agents, particularly oral
antibiotics, tends to have minimal effects on CSF cytology [27,52-55]. However, CSF chemistry results in
pretreated patients must be interpreted with caution. In a retrospective review of 231 children with bacterial
meningitis in the post-Hib and pneumococcal conjugate vaccine era, 85 children received antibiotics before LP
[55]. Receipt of antibiotics for ≥12 hours before LP was associated with increased median CSF glucose
concentration (48 versus 29 mg/dL [2.66 versus 1.6 mmol/L]) and decreased median CSF protein concentration
(121 versus 178 mg/dL [1.21 versus 1.78 g/L]) [55].

Although the use of antimicrobial therapy before LP affects the CSF culture and perhaps the Gram stain
[27,44,54], conventional teaching has been that a pathogen still can be identified in the CSF in the majority of
patients up to several hours after the administration of antibiotics [27]. However, a review of 128 children with
bacterial meningitis specifically addressed this question and found that the time interval between antibiotic
administration and negative CSF cultures may be shorter than appreciated for children who receive parenteral
antibiotics [44]:

● Among children with meningococcal meningitis who were treated with a parenteral dose of an extended-
spectrum cephalosporin, three of nine LPs were sterile within one hour (occurring as early as 15 minutes),
and all were sterile by two hours.
 ● Sterilization of the CSF was slower with pneumococcal meningitis. The first negative culture was obtained
four hours after administration of antibiotics, and five of seven were negative by 10 hours.

Additional cultures — Culture of other sites should be obtained as indicated [10].

● Gram stain and culture of petechial or purpuric lesions may identify the causative agent [10].

● Urine cultures should be obtained in infants (<12 months of age) who present with fever and nonspecific
symptoms and signs of meningitis, since urinary tract infection may be the primary source of the meningitis
pathogen in such patients [10,56]. However, it is common to note a CSF pleocytosis in infants with urinary
tract infection and sterile CSF cultures [56-60]. In such cases, the CSF pleocytosis may be related to a viral
meningitis [61] or an innate response to bacteria or bacterial products [62,63].

Urine cultures also should be obtained in children with anomalies of the urinary tract and in
immunocompromised patients. (See 'Predisposing factors' above.)

If possible, urine for culture should be obtained before antimicrobial therapy is administered. However,
therapy should not be withheld if an adequate specimen cannot be promptly obtained [10].

● In patients with concomitant otitis media, Gram-stained smear of middle ear fluid (obtained by needle
aspiration) may permit immediate identification of the likely pathogen and may be helpful if the Gram-
stained smear of the CSF is equivocal [10].

● Cultures of the nose and throat are not helpful in identifying the etiology of bacterial meningitis [10].

Other tests — Other tests for the diagnosis of bacterial meningitis have limited availability and/or undetermined
utility for early diagnosis, as illustrated below.

● Serum C-reactive protein is a marker of infection and inflammation, but is nonspecific.

● In retrospective cohorts, elevated serum procalcitonin (>0.5 ng/mL) appears to be helpful in distinguishing
bacterial from viral meningitis, but additional data are necessary before procalcitonin can be included in
clinical decision rules [64,65].

● The presence of tumor necrosis factor in CSF may distinguish bacterial from viral meningitis [66], but this
assay is not generally available.

● The presence of IL-1 or IL-10 in CSF also may correlate with meningitis, but whether these indicators are
sensitive and specific enough to accelerate the diagnosis remains to be determined [67].

The possibility of an immune deficiency should be considered in children who develop Hib meningitis or
pneumococcal meningitis with a serotype contained in the pneumococcal vaccine despite having received at
least three doses of the respective conjugate vaccines. In such children, it is reasonable to screen for
underlying immune deficiency, particularly if there are additional concerning features in the history or physical
examination (eg, recurrent infections, poor growth). The evaluation may include measuring quantitative
immunoglobulins and complement activity and examining peripheral blood smear for Howell-Jolly bodies
(picture 10). The presence of Howell-Jolly bodies most frequently indicates either absence of the spleen (eg,
surgical removal) or splenic hypofunction. If an unusual organism, such as S. aureus or another organism that
commonly colonizes the skin, is isolated, a direct connection to the skin via a sinus tract should be sought [68].
An overview of primary immunodeficiencies and an approach to the diagnosis of splenic dysfunction are found
elsewhere. (See "Primary humoral immunodeficiencies: An overview".)
IMAGING

It is not uncommon for lumbar puncture (LP) to be delayed while a computed tomographic (CT) scan is
performed to exclude an intracranial process that would contraindicate an LP. Although concerns exist about
herniation following LP in children, a review of the literature found that herniation was unlikely in children with
bacterial meningitis unless they had focal neurologic findings or coma; furthermore, a normal CT does not
absolutely exclude subsequent herniation [69,70].

Indications for imaging before LP in children with suspected bacterial meningitis include (table 4) [40]:

● Coma
● The presence of a cerebrospinal fluid (CSF) shunt
● History of hydrocephalus
● Recent history of CNS trauma or neurosurgery
● Papilledema
● Focal neurologic deficit (with the exception of palsy of cranial nerve VI [abducens nerve] or VII [facial
nerve])

In children who require neuroimaging before LP, blood cultures should be obtained and empiric antibiotics
administered before imaging (table 4) [40]. LP should be performed as soon as possible after neuroimaging
provided that neuroimaging has not revealed any contraindications.

DIAGNOSIS

Acute bacterial meningitis should be suspected in children who present with fever and signs of meningeal
inflammation. In infants, the clinical manifestations may include fever, hypothermia, lethargy, respiratory
distress, jaundice, poor feeding, vomiting, diarrhea, seizures, restlessness, irritability, and/or bulging fontanel
[10,17]. In older children, clinical manifestations may include fever, headache, photophobia, nausea, vomiting,
confusion, lethargy, and/or irritability [10,14]. Previous receipt of oral antibiotics does not affect the clinical
presentation of acute bacterial meningitis. (See 'Presentation' above.)

Isolation of a bacterial pathogen from the cerebrospinal fluid (CSF) (by culture or other diagnostic techniques)
confirms the diagnosis of bacterial meningitis. Isolation of bacteria from blood cultures in a patient with CSF
pleocytosis also confirms the diagnosis, even if the CSF culture remains negative.

Supportive findings include CSF pleocytosis with a predominance of neutrophils, decreased CSF glucose
concentration (or ratio of CSF to blood glucose), elevated CSF protein, and isolation of the same pathogen from
blood culture (table 5). However, because CSF and blood cultures may be obtained at different points in time
during the evolution of the disease process, varying combinations of positive or negative cultures of blood and
CSF and the presence or absence of pleocytosis are possible [10,12]. (See 'Laboratory evaluation' above.)

The CSF culture may be negative in children who received antibiotic therapy before CSF examination. In such
children, increased CSF cell count with a predominance of neutrophils, elevated CSF protein concentration,
and/or decreased CSF glucose concentration usually are sufficient to establish the diagnosis of bacterial
meningitis [27,52-54]; blood cultures and/or rapid diagnostic tests may help to identify the pathogenic organism.
(See 'Interpretation of CSF in pretreated patients' above.)

DIFFERENTIAL DIAGNOSIS
The clinical and laboratory findings of bacterial meningitis overlap with those of meningitis caused by viruses,
mycobacteria, fungi, or protozoa (table 5). Other processes that can mimic bacterial meningitis include central
nervous system (CNS) abscess, bacterial endocarditis with embolism, subdural empyema, and brain tumor
[14,19]. Differentiation of these disorders from bacterial meningitis requires careful examination of cerebrospinal
fluid (CSF) and neuroimaging.

CSF pleocytosis — The Bacterial Meningitis Score (BMS) is a clinical prediction rule for children with CSF
pleocytosis (CSF white blood cell [WBC] count ≥10 cells/microL) that classifies children who have not been
pretreated with antibiotics at "very low risk of bacterial meningitis" if they meet all of the following criteria [71]:

● Negative CSF Gram stain

● CSF absolute neutrophil count (ANC) <1000 cells/microL
● CSF protein of <80 mg/dL
● Peripheral blood ANC of <10,000 cells/microL
● No history of seizure before or at the time of presentation

In a meta-analysis of data from eight validation studies (one of which was prospective) including 5312 patients,
bacterial meningitis was diagnosed in 23 percent [72]. The BMS missed nine patients with bacterial meningitis:
three were younger than two months, three had petechiae or purpura, and three were older than two months
and did not have petechiae or purpura; the six patients who were older than two months all had N. meningitidis.
In pooled analysis, the sensitivity and specificity of the BMS for bacterial meningitis were 99.3 percent (95% CI
98.7-99.7 percent) and 62.1 percent (60.5 to 63.7 percent), respectively.

These findings suggest that the BMS may be used in conjunction with clinical judgment to identify children with
CSF pleocytosis who are at very low risk of bacterial meningitis and to assist clinical decision making. To avoid
misclassification, the BMS should not be used in children who are younger than two months,
immunocompromised, ill-appearing, have been pretreated with antibiotics, have petechiae or purpura on
examination, have a ventriculoperitoneal shunt, or have recently had neurosurgery [71,72].

Normal CSF findings — In a review of 650 children (0 to 12 years) who underwent lumbar puncture (LP) for
evaluation of possible meningitis, CSF findings were normal in 57 percent of patients [19]. Indications for LP
included fever; headache; vomiting; nuchal rigidity; first episode of convulsion with fever; and encephalopathic,
toxic, or septic appearance. The incidence of normal CSF varied according to age, occurring in 83 percent of
infants 0 to 8 weeks, 65 percent of children 8 weeks to 24 months, 53 percent of children 2 to 5 years, and 37
percent of children 5 to 12 years.

Common conditions among children with normal CSF findings included:

● Right-sided pneumonia
● Otitis media (most presented with fever and irritability)
● Pharyngitis/tonsillitis
● Upper respiratory infection with cervical adenopathy
● Viral infection/herpangina (predominantly in children <5 years)
● Gastroenteritis

Other important causes of nuchal rigidity that should be considered in children evaluated for meningitis who
have normal CSF findings include retropharyngeal abscess and cervical spine injury or infection (table 6). (See
"Approach to neck stiffness in children".)
Important causes of altered or depressed mental status in children include head trauma, seizure, stroke, and
ingestions (table 7). (See "Evaluation of stupor and coma in children" and "Approach to the child with occult
toxic exposure".)

INITIATION OF EMPIRIC THERAPY

Empiric therapy for bacterial meningitis should be initiated immediately after the results of lumbar puncture (LP)
are received or immediately after the LP is performed.

It is essential that antimicrobial therapy not be delayed if there is a contraindication to or inability to perform an
LP. If LP is delayed by the need for cranial imaging, blood cultures should be obtained and empiric antibiotic
therapy administered before the imaging study (table 4). (See 'Imaging' above.)

Empiric treatment consists of bactericidal agent(s) that achieve significant levels in the cerebrospinal fluid
(CSF), usually a third-generation cephalosporin and vancomycin. More specific treatment can be instituted
when the etiologic agent is identified. (See "Bacterial meningitis in children older than one month: Treatment
and prognosis", section on 'Empiric therapy'.)

Children in whom bacterial meningitis is suspected, or in whom bacterial meningitis cannot be excluded, based
upon initial CSF findings should be admitted to the hospital.

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions around the world
are provided separately. (See "Society guideline links: Bacterial meningitis in infants and children".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics
patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the
four or five key questions a patient might have about a given condition. These articles are best for patients who
want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education
pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade
reading level and are best for patients who want in-depth information and are comfortable with some medical
jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these
topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on
"patient info" and the keyword[s] of interest.)

● Basics topics (see "Patient education: Meningitis in children (The Basics)" and "Patient education: Bacterial
meningitis (The Basics)")

● Beyond the Basics topic (see "Patient education: Meningitis in children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

 ● Streptococcus pneumoniae and Neisseria meningitidis are the most common causes of bacterial meningitis
in infants and children older than one month of age. (See 'Causative organisms' above.)

● Certain host factors may predispose to bacterial meningitis with a particular organism (table 2). Additional
risk factors for bacterial meningitis include exposure to someone with meningococcal or Haemophilus
influenzae type b (Hib) meningitis, cochlear implantation device, recent neurosurgical procedure, or
anatomic defect (dermal sinus or urinary tract anomaly). (See 'Predisposing factors' above.)

● Most patients with bacterial meningitis present with fever and symptoms and signs of meningeal
inflammation (movie 1A-B). However, the clinical manifestations of bacterial meningitis are variable and
nonspecific; no single sign is pathognomonic. (See 'Clinical features' above.)

● Suspected bacterial meningitis is a medical emergency, and immediate diagnostic steps must be taken to
establish the specific cause (table 4). (See 'Evaluation' above.)

● The laboratory evaluation of children with suspected meningitis should include a complete blood count with
differential and platelet count, two aerobic blood cultures, and serum electrolytes, glucose, blood urea
nitrogen, and creatinine. Evaluation of clotting function is especially indicated if petechiae or purpuric
lesions are noted. (See 'Blood tests' above.)

● A lumbar puncture should be performed on any child in whom, after careful history and physical
examination, the diagnosis of meningitis is suspected unless specific contraindications to lumbar puncture
are present. Examination of the cerebrospinal fluid (CSF) should include cell count and differential, glucose
and protein concentration, Gram stain, and culture. (See 'CSF examination' above.)

● If there is a contraindication to or inability to perform a lumbar puncture or if the lumbar puncture is delayed
by the need for cranial imaging, blood cultures should be obtained and empiric antibiotics administered as
soon as possible. (See 'CSF examination' above.)

● Laboratory findings characteristic of bacterial meningitis include CSF pleocytosis with a predominance of
neutrophils, elevated CSF protein, decreased CSF glucose, the presence of an organism on CSF Gram
stain, and isolation of a pathogenic organism from the CSF and/or blood culture (table 5). (See
'Interpretation of CSF' above.)

● Isolation of a bacterial pathogen from the CSF (by culture or other diagnostic techniques) confirms the
diagnosis of bacterial meningitis. (See 'Diagnosis' above.)

● In children who were treated with antibiotics before CSF was obtained, increased CSF cell count, elevated
CSF protein concentration, and/or decreased CSF glucose concentration usually are sufficient to establish
the diagnosis of meningitis; blood cultures and/or rapid diagnostic tests may help to identify the pathogenic
organism. (See 'Interpretation of CSF in pretreated patients' above.)

● Empiric therapy for bacterial meningitis (a third-generation cephalosporin and vancomycin) should be
initiated immediately after the results of lumbar puncture are received or immediately after the lumbar
puncture is performed if the clinical suspicion for bacterial meningitis is high. (See 'Initiation of empiric
therapy' above and "Bacterial meningitis in children older than one month: Treatment and prognosis",
section on 'Empiric therapy'.)

Use of UpToDate is subject to the Subscription and License Agreement.

Topic 5968 Version 35.0

GRAPHICS

Characteristic features of common causes of bacterial meningitis

Organism Site of entry Age range Predisposing conditions

Neisseria Nasopharynx All ages Usually none, rarely complement deficiency

meningitidis

Streptococcus Nasopharynx, direct extension All ages All conditions that predispose to pneumococcal
pneumoniae across skull fracture, or from bacteremia, fracture of cribriform plate, cochlear
contiguous or distant foci of implants, cerebrospinal fluid otorrhea from basilar skull
infection fracture, defects of the ear ossicle (Mondini defect)

Listeria Gastrointestinal tract, placenta Older adults and Defects in cell-mediated immunity (eg, glucocorticoids,
monocytogenes neonates transplantation [especially renal transplantation]),
pregnancy, liver disease, alcoholism, malignancy

Coagulase- Foreign body All ages Surgery and foreign body, especially ventricular drains
negative
staphylococci

Staphylococcus Bacteremia, foreign body, skin All ages Endocarditis, surgery and foreign body, especially
aureus ventricular drains; cellulitis, decubitus ulcer

Gram-negative Various Older adults and Advanced medical illness, neurosurgery, ventricular
bacilli neonates drains, disseminated strongyloidiasis

Haemophilus Nasopharynx, contiguous Adults; infants Diminished humoral immunity

influenzae spread from local infection and children if not
vaccinated

Graphic 73706 Version 8.0

Host immune defects predisposing to meningitis

Frequency of defect actually leading to

Host problem Organism favored
infection

Absence of opsonizing Streptococcus pneumoniae Common in all age groups

antibody
Haemophilus influenzae Common in very young children

Asplenia: surgical or S. pneumoniae Rare

functional
Neisseria meningitidis Very rare

Complement deficiency N. meningitidis Very rare

Glucocorticoid excess Listeria monocytogenes Rare

Cryptococcus neoformans Rare

HIV infection C. neoformans About 5 percent eventually get cryptococcal

meningitis

S. pneumoniae Common presenting illness

L. monocytogenes Rare

Bacteremia/endocarditis Staphylococcus aureus; various gram- Rare

negative rods

Basilar skull fracture S. pneumoniae; other upper respiratory Very rare

tract flora

HIV: human immunodeficiency virus.

Graphic 72293 Version 8.0

Etiology of bacterial meningitis in 231 children from 20 pediatric emergency
departments, United States 2001-2004

%: percent.
* Citrobacter diversus, Enterobacter cloacae, Klebsiella spp, Pasteurella multocida, Pseudomonas aeruginosa,
Salmonella spp.
• Listeria monocytogenes (2 percent); group A streptococcus (2 percent), Moraxella catarrhalis (0.4 percent).

Data from: Nigrovic LE, Kuppermann N, Malley R. Children with bacterial meningitis presenting to the emergency
department during the pneumococcal conjugate vaccine era. Acad Emerg Med 2008; 15:522.

Graphic 60662 Version 4.0

Dermal sinus

Dermal sinus lesions may predispose to meningitis with Staphylococcus aureus,

Coagulase-negative staphylococci, and enteric Gram-negative organisms, such
as Escherichia coli and Klebsiella species.

Courtesy of Sheldon L Kaplan, MD.

Graphic 79563 Version 2.0

Glasgow Coma Scale and Pediatric Glasgow Coma Scale

Glasgow Coma
Sign Pediatric Glasgow Coma Scale [2] Score
Scale [1]

Eye opening Spontaneous Spontaneous 4

To command To sound 3

To pain To pain 2

None None 1

Verbal Oriented Age-appropriate vocalization, smile, or orientation to sound, interacts (coos, 5

response babbles), follows objects

Confused, disoriented Cries, irritable 4

Inappropriate words Cries to pain 3

Incomprehensible sounds Moans to pain 2

None None 1

Motor Obeys commands Spontaneous movements (obeys verbal command) 6

response
Localizes pain Withdraws to touch (localizes pain) 5

Withdraws Withdraws to pain 4

Abnormal flexion to pain Abnormal flexion to pain (decorticate posture) 3

Abnormal extension to pain Abnormal extension to pain (decerebrate posture) 2

None None 1

Best total score 15

The Glasgow Coma Scale (GCS) is scored between 3 and 15, 3 being the worst, and 15 the best. It is composed of three
parameters: best eye response (E), best verbal response (V), and best motor response (M). The components of the GCS should be
recorded individually; for example, E2V3M4 results in a GCS of 9. A score of 13 or higher correlates with mild brain injury, a score
of 9 to 12 correlates with moderate injury, and a score of 8 or less represents severe brain injury. The pediatric Glasgow coma
scale (PGCS) was validated in children two years of age or younger.

Data from:
1. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974; 2:81.
2. Holmes JF, Palchak MJ, MacFarlane T, Kuppermann N. Performance of the pediatric Glasgow coma scale in children with blunt head
trauma. Acad Emerg Med 2005; 12:814.

Graphic 59662 Version 12.0

Petechiae

Courtesy of Leslie Raffini, MD.

Graphic 73905 Version 2.0

Acute meningococcemia

Skin lesions in acute meningococcemia can begin as papules but quickly

progress to petechiae and purpura. As seen here, the purpuric lesions can
coalesce.

Courtesy of Charles V Sanders. (The Skin and Infection: A Color Atlas and Text,
Sanders CV, Nesbitt, LT Jr [Eds], Williams & Wilkins, Baltimore, 1995).

Graphic 52107 Version 6.0

Magnetic resonance images of bilateral subdural empyema in a child with Haemophilus
influenzae meningitis

(Panel A) Post-contrast T1 weighted axial image demonstrating leptomeningeal and dural enhancement (arrows) with hypointense
subdural collection.
(Panel B) Flair axial image demonstrating hyperintense proteinaceous subdural collections (dashed arrows) overlying bifrontal lobe
surfaces.

Courtesy of Sherri B Birchansky, MD, Texas Children's Hospital and Baylor College of Medicine.

Graphic 117506 Version 1.0

Bifrontal craniotomy for drainage of bilateral subdural empyema

Intraoperative photograph of a child undergoing bifrontal craniotomy for drainage of bilateral subdural empyema. Note the
extensive purulent material over the surface of the exposed brain. Thrombosed superficial veins are also visible (arrow). The
child developed subdural empyema as a complication of Haemophilus influenzae meningitis.

Courtesy of Sandi K Lam, MD, MBA, Texas Children's Hospital and Baylor College of Medicine.

Graphic 117505 Version 1.0

Rapid overview: Emergency management of infants (≥1 month) and children with suspected
bacterial meningitis

Clinical findings
Infants: Fever, hypothermia, bulging fontanel, lethargy, irritability, seizures, respiratory distress, poor feeding, vomiting.

Older children: Fever, headache, photophobia, meningismus, nausea/vomiting, confusion, lethargy, irritability.

Evaluation
Laboratory testing – Initial laboratory testing should include (STAT):
◾ Blood cultures (two sets).
◾ CBC with differential and platelet count.
◾ Serum electrolytes, BUN, creatinine, glucose.
◾ PT, INR, and PTT.

Lumbar puncture:
◾ LP should be performed in all children with suspected meningitis unless there is a specific contraindication to LP.
◾ Contraindications to LP include: Cardiopulmonary compromise, clinical signs of increased intracranial pressure, papilledema,
focal neurologic signs, and skin infection over the site for LP. If there is a contraindication to or inability to perform an LP, or
if the LP is delayed by the need for cranial imaging, antimicrobial therapy should not be delayed. Blood cultures should be
obtained and empiric antibiotics administered as soon as is possible.
◾ CSF should be sent for the following (STAT): Cell count and differential, glucose and protein concentration, Gram stain, and
culture.

Neuroimaging (eg, head CT):

◾ In children who require neuroimaging before LP, blood cultures should be obtained and empiric antibiotics
administered before imaging. LP should be performed as soon as possible after neuroimaging is completed, provided
that the imaging has not revealed any contraindications.
◾ Indications for neuroimaging before LP include: Severely depressed mental status (coma), papilledema, focal neurologic
deficit (with the exception of cranial nerve VI or VII palsy), history of hydrocephalus and/or presence of a CSF shunt, recent
history of CNS trauma or neurosurgery.

Management
Supportive care:
◾ Ensure adequate oxygenation, ventilation, and circulation.
◾ Obtain venous access and initiate cardiorespiratory monitoring while obtaining laboratory studies.
◾ Keep the head of bed elevated at 15 to 20 degrees.
◾ Treat hypoglycemia, acidosis, and coagulopathy, if present.

Antimicrobial therapy – Antibiotic therapy should be initiated immediately following the LP if the clinical suspicion for meningitis
is high:
◾ Administer first dose of empiric antimicrobial therapy:
• Vancomycin (15 mg/kg IV), plus
• Ceftriaxone (50 mg/kg IV) or cefotaxime (100 mg/kg IV; where available).
◾ Consider dexamethasone therapy* (0.15 mg/kg IV) in patients with certain risk factors (eg, unimmunized patients, young
children [age ≥6 weeks to ≤5 years], children with sickle cell disease, asplenic patients) or if there is known or suspected
Haemophilus influenzae infection (eg, based on Gram stain results).
◾ If dexamethasone is given, it should be administered before, or immediately after, the first dose of antimicrobial therapy.

STAT: intervention should be performed emergently; CBC: complete blood count; BUN: blood urea nitrogen; PT: prothrombin time; INR:
international normalized ratio; PTT: partial thromboplastin time; LP: lumbar puncture; CSF: cerebrospinal fluid; CT: computed tomography;
CNS: central nervous system; IV: intravenous.
* Decisions regarding the administration of dexamethasone should be individualized. The use of dexamethasone in children with suspected
meningitis is controversial, and the opinions of UpToDate authors regarding this issue differ. One UpToDate author would administer
dexamethasone only to children who are known or highly suspected to have H. influenzae (Hib) at the time the LP is performed (a fairly
uncommon scenario), whereas another UpToDate author would administer dexamethasone to all young children (age ≥6 weeks to ≤5 years
old) with community-acquired meningitis and to children with sickle cell disease or asplenia with suspected bacterial meningitis. The 2015
Red Book statement on dexamethasone use in pneumococcal meningitis also acknowledges that expert opinion differs on this issue.
Evidence supporting the efficacy of dexamethasone in reducing the risk of hearing loss in children with meningitis is most clearly
established for infections caused by Hib. For other bacterial pathogens (eg, pneumococcus, meningococcus), the efficacy of dexamethasone
is uncertain. For further details, refer to UpToDate topics on bacterial meningitis in children, pneumococcal meningitis in children, and the
use of dexamethasone and other measures to prevent neurologic complications of pediatric bacterial meningitis.

Graphic 74865 Version 10.0

Typical cerebrospinal fluid findings in central nervous system infections*

Total white blood cell count

Glucose (mg/dL) Protein (mg/dL)
(cells/microL)

<10 ¶ 10 to 40 Δ 100 to 500 ◊ 50 to 300 § >1000 100 to 1000 5 to 100

More Bacterial Bacterial Bacterial Viral meningitis Bacterial Bacterial or Early

common meningitis meningitis meningitis Nervous system meningitis viral bacterial
Lyme disease meningitis meningitis
(neuroborreliosis) TB meningitis Viral
Encephalitis meningitis

Neurosyphilis Neurosyphilis

TB meningitis ¥ TB meningitis

Less TB meningitis Neurosyphilis Some cases Encephalitis Encephalitis

common Fungal Some viral of mumps
meningitis infections and LCMV
(such as
mumps and
LCMV)

TB: tuberculosis; LCMV: lymphocytic choriomeningitis virus.

* It is important to note that the spectrum of cerebrospinal fluid values in bacterial meningitis is so wide that the absence of one or more
of these findings is of little value. Refer to the UpToDate topic reviews on bacterial meningitis for additional details.
¶ <0.6 mmol/L.
Δ 0.6 to 2.2 mmol/L.
◊ 1 to 5 g/L.
§ 0.5 to 3 g/L.
¥ Cerebrospinal fluid protein concentrations may be higher in some patients with tuberculous meningitis; concentrations >500 mg/dL are
an indication of blood-brain barrier disruption or increased intracerebral production of immunoglobulins, and extremely high concentrations,
in the range of 2 to 6 g/dL, may be found in association with subarachnoid block.

Graphic 76324 Version 10.0

Streptococcus pneumoniae in cerebrospinal fluid

Gram stain of cerebrospinal fluid (x1000) shows inflammatory cells and gram-
positive diplococci. Streptococcus pneumoniae grew from this specimen.

Courtesy of Harriet Provine.

Graphic 72926 Version 5.0

Neisseria meningitidis in cerebrospinal fluid

Gram stain of cerebrospinal fluid (x1000) shows inflammatory cells and kidney-
shaped, gram-negative diplococci (arrows). Neisseria meningitidis grew from
this specimen.

Courtesy of Harriet Provine.

Graphic 61788 Version 4.0

Haemophilus influenzae in cerebrospinal fluid

Gram stain of cerebrospinal fluid (x1000) shows inflammatory cells and small,
pleomorphic, gram-negative coccobacilli. Haemophilus influenzae grew from this
specimen.

Courtesy of Harriet Provine.

Graphic 52680 Version 5.0

Group B Streptococcus in cerebrospinal fluid

Gram stain of cerebrospinal fluid (x1000) shows inflammatory cells and gram-
positive coccobacilli. Streptococcus agalactiae (group B Streptococcus) grew
from this specimen.

Courtesy of Harriet Provine.

Graphic 72503 Version 4.0

Listeria monocytogenes in cerebrospinal fluid

Gram stain of cerebrospinal fluid (x1000) shows inflammatory cells and small,
gram-positive rods and coccobacilli. Culture of this specimen revealed
moderate-sized beta-hemolytic colonies composed of small, motile gram-
positive rods, confirmed to be Listeria monocytogenes.

Courtesy of Harriet Provine.

Graphic 79633 Version 6.0

Howell-Jolly bodies following splenectomy

This peripheral blood smear shows 2 red blood cells (RBCs) that contain Howell-
Jolly bodies (arrowheads). Howell-Jolly bodies are remnants of RBC nuclei that
are normally removed by the spleen. Thus, they are seen in patients who have
undergone splenectomy (as in this case) or who have functional asplenia (eg,
from sickle cell disease). Target cells (arrows) are another consequence of
splenectomy.

Courtesy of Carola von Kapff, SH (ASCP).

Graphic 60588 Version 8.0

Normal peripheral blood smear

High-power view of a normal peripheral blood smear. Several platelets

(arrowheads) and a normal lymphocyte (arrow) can also be seen. The red
cells are of relatively uniform size and shape. The diameter of the normal red
cell should approximate that of the nucleus of the small lymphocyte; central
pallor (dashed arrow) should equal one-third of its diameter.

Courtesy of Carola von Kapff, SH (ASCP).

Graphic 59683 Version 5.0

Causes of neck stiffness in children

Trauma
Clavicular fracture*

Epidural hematoma of the cervical spine ¶

Fracture of the cervical spine ¶

Muscular contusion or neck spasm*

SCIWORA syndrome ¶

Subarachnoid hemorrhage ¶

Subluxation of the cervical spine ¶

Infectious or inflammatory
Bacterial meningitis ¶

Branchial cleft or thyroglossal duct cyst abscess

Cervical lymphadenitis*

Collagen vascular disease (eg, systemic JIA, ankylosing spondylitis, psoriatic arthritis)

Infections of the spine: vertebral osteomyelitis, infectious discitis, epidural abscess ¶

Intervertebral disc calcification

Kawasaki disease with cervical lymphadenopathy

Lyme meningitis

Muscle strain*

Otitis media and mastoiditis

Pharyngitis or tonsillitis*

Retropharyngeal abscess ¶

Rotary atlantoaxial subluxation as a result of local inflammation or procedure (Grisel's syndrome)

Upper lobe pneumonia

Viral meningitis*

Viral myositis

Tumors, other space-occupying and vascular lesions of the central nervous system
Brain tumor ¶

Other space-occupying lesions of the spinal cord (neurenteric cyst, arteriovenous malformation, syringomyelia) ¶

Other tumors of the head and neck (osteoid osteoma, eosinophilic granuloma, orbital tumor, acoustic neuroma, osteoblastoma,
metastatic tumor to the spine, nasopharyngeal carcinoma, bone cyst) ¶

Spinal cord tumor ¶

Subarachnoid hemorrhage (aneurysm rupture-congenital, sickle cell disease) ¶

Congenital conditions
Atlantoaxial instability secondary to congenital conditions (Down's syndrome, Klippel-Feil syndrome, os odontoideum, Morquio's
syndrome)

Benign paroxysmal torticollis

Congenital muscular torticollis*

Skeletal malformations (Klippel-Feil syndrome, Sprengel's deformity, hemiatlas, basilar impression, occipitocervical synostosis)

Miscellaneous
Dystonic reaction

Guillain-Barre syndrome

Myasthenia gravis

Ophthalmologic, neurologic, and/or vestibular causes (strabismus, cranial nerve palsies, extraocular muscle palsies, refractive
errors, myasthenia gravis, Guillain-Barre syndrome, migraine headaches)

Pseudo-tumor cerebri

Psychogenic

Sandifer syndrome

Spasmus nutans

Spontaneous pneumomediastinum
JIA: juvenile idiopathic arthritis; SCIWORA: spinal cord injury without radiographic abnormality.
* Common condition.
¶ Life-threatening condition.

Graphic 67226 Version 10.0

Causes of coma

I. Symmetrical, nonstructural II. Symmetrical, structural

Toxins Supratentorial

Lead Bilateral internal carotid occlusion

Thallium Bilateral anterior cerebral artery occlusion

Mushrooms Sagittal sinus thrombosis

Cyanide Subarachnoid hemorrhage

Methanol Thalamic hemorrhage*

Ethylene glycol Trauma-contusion, concussion*

Carbon monoxide Hydrocephalus

Drugs Infratentorial

Sedatives Basilar occlusion*

Barbiturates* Midline brainstem tumor

Other hypnotics Pontine hemorrhage*

Tranquilizers Central pontine myelinolysis

Bromides III. Asymmetrical, structural

Alcohol
Supratentorial
Opiates
Thrombotic thrombocytopenic purpura ¶
Paraldehyde
Disseminated intravascular coagulation
Salicylate
Nonbacterial thrombotic endocarditis (marantic endocarditis)
Psychotropics
Subacute bacterial endocarditis
Anticholinergics
Fat emboli
Amphetamines
Unilateral hemispheric mass (tumor, abscess, bleed) with
Lithium herniation

Phencyclidine Subdural hemorrhage bilateral

Monoamine oxidase inhibitors Intracerebral bleed

Metabolic Pituitary apoplexy ¶

Hypoxia Massive or bilateral supratentorial infarction

Hypercapnia Multifocal leukoencephalopathy

Hypernatremia* Creutzfeldt-Jakob disease

Hypoglycemia* Adrenal leukodystrophy

Hyperglycemic nonketotic coma Cerebral vasculitis

Diabetic ketoacidosis Cerebral abscess

Lactic acidosis Subdural empyema

Hypercalcemia Thrombophlebitis ¶

Hypocalcemia Multiple sclerosis

Hypermagnesemia Leukoencephalopathy associated with chemotherapy

Hyperthermia Acute disseminated encephalomyelitis

Hypothermia Infratentorial

Reye syndrome Brainstem infarction

Aminoacidemia Brainstem hemorrhage

Wernicke encephalopathy Brainstem thrombencephalitis

Porphyria

Hepatic encephalopathy*

Uremia

Dialysis encephalopathy

Addisonian crisis

Hypothyroidism

Infections

Bacterial meningitis

Viral encephalitis
 Postinfectious encephalomyelitis

Syphilis

Sepsis

Typhoid fever

Malaria

Waterhouse-Friderichsen syndrome

Psychiatric

Catatonia

Other

Postictal seizure*

Diffuse ischemia (myocardial infarction, heart failure,

arrhythmia)

Hypotension

Fat embolism*

Hypertensive encephalopathy

Hypothyroidism

Nonconvulsive status epilepticus

Heat stroke

* Relatively common asymmetrical presentation.

¶ Relatively symmetrical presentation.

Reproduced with permission from: Berger JR. Clinical Approach to Stupor and Coma. In: Neurology in Clinical Practice: Principles of
Diagnosis and Management, 4th ed, Bradley WG, Daroff RB, Fenichel GM, Jankovic J (Eds), Butterworth Heinemann, Philadelphia, PA 2004.
p.46. Copyright © 2004 Elsevier.

Graphic 65571 Version 5.0

Contributor Disclosures
Sheldon L Kaplan, MD Grant/Research/Clinical Trial Support: Pfizer [Streptococcus pneumoniae]; Merck [Staphylococcus
aureus]; MeMed Diagnostics [Bacterial and viral infections]. Consultant/Advisory Board: Pfizer [Staphylococcus aureus].
Other Financial Interest: Pfizer [PCV13; linezolid]; Medscape [Bacterial meningitis]; Elsevier [Pediatric infectious
diseases]. Morven S Edwards, MD Grant/Research/Clinical Trial Support: Pfizer [Group B Streptococcus]. Douglas R
Nordli, Jr, MD Consultant/Advisory Boards: Eisai Pharmaceuticals [Neurology]. Carrie Armsby, MD, MPH Nothing to
disclose

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